Breast cancer pre- and post-treatment gene expresion anlyses

Introduction: Paper and background

  • Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer
Neoadjuvant chemotherapy (NACT) an increasingly used approach for treatment of breast cancer
Circulating Exosomal microRNAs(miRNA) small RNA molecules circulating in bodily fluids, potentially serving as biomarkers for treatment response after NACT
Pathological Complete Response (pCR) absence of active cancer cells in a tissue from the tumor site after NACT
Non-Pathological Complete Response (non-pCR) presence of active cancer cells in a tissue from the tumor site after the treatment
  • The purpose of the study: to investigate whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT

Todorova, Valentina K., et al. “Circulating exosomal microRNAs as predictive biomarkers of neoadjuvant chemotherapy response in breast cancer.” Current Oncology 29.2 (2022): 613-630.

Introduction: pCR & nonpCR

Materials and methods: Flowchart

Methods: Metadata & Describe

Methods: Describe

Methods: Gene Expression Analysis

Methods: Virtual pull-down and Gene Enrichement Analysis

  • Virtual pull-down:
library(DiscoNet)
network_pCR <- virtual_pulldown(
  seed_nodes = seed, 
  database = string_database, 
  id_type = "hgnc", 
  string_confidence_score = 700) # default value
  • Community detection
library(DiscoNet)
communities_list <- community_detection(
  graph_object, 
  algorithm = "mcode", # specifies algorithm, in this case MCODE
  D = 0.05, # threshold of weight percentage of the vertex to be use by MCODE standard value
  haircut = TRUE) # removes the nodes that are only connected to a single node in the community detected
  • Over representation analysis
library(fgsea)

ora_result_nonpCR <- fora(
    pathways = biological_process_list, 
    genes = gense_in_each_community, 
    universe = all_genes_in_analysis, 
    minSize = 10
)

Results: Gene Expression Analysis

Results: Virtual pull-down

  • Pre vs. Post Treatment:
    • The nonpCR Group has 5 potential complexes or networks with upregulated or downregulated activity when comparing pre and post treatment
    • The nonpCR Group has 11 potential complexes or networks with upregulated or downregulated activity when comparing pre- and post-treatment

Results: Gene Enrichment Analysis

  • For each network the main enriched biological processes were identified

  • This is just a representative plot:

Discussion and Conclusion